title: Pursuing type 1 diabetes mellitus and related complications through urinary proteomics.
abstract: Diabetes mellitus is a chronic metabolic disease with multiple complications, and its successful management requires early diagnosis, to allow timely interventions. Here, we have comprehensively analyzed the proteome changes in urine of type 1 diabetic subjects with and without complications such as retinopathy and nephropathy. gel electrophoresis combined to liquid chromatography-tandem mass spectrometry (GeLC-MS/MS) analysis of midstream urine highlighted the mechanisms involved in disease pathogenesis as, for instance wound healing and blood coagulation in all diabetics or altered ganglioside metabolism in retinopathy, and also some urinary proteins with potential diagnosis value. From these, gelsolin and antithrombin-III appear as promising diagnosis markers for type 1 diabetes mellitus (T1DM), whereas ephrin type-B receptor 4 and vitamin K-dependent protein Z seem to be promising markers for advanced T1DM disease state presenting retinopathy and nephropathy (T1DM-R + N). Data also suggest urinary ganglioside GM2 activator and beta-hexosaminidase subunit beta as potential urinary markers of retinopathy in diabetics. Taken together, the present exploratory urinary proteomic analysis might be seen as an important starting point for studies targeting specific urinary proteins aimed at the implementation of new biomarkers for the early detection of T1DM-related microvascular complications.
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal; College of Health Technology of Coimbra, Polytechnic Institute of Coimbra, Coimbra, Portugal.
authors.forename: Armando
authors.initials: A
authors.lastname: Caseiro
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Barros
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Padrão
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Aroso
authors.affiliation: Internal Medicine Service, Figueira da Foz Hospital, Figueira da Foz, Portugal.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Quintaneiro
authors.affiliation: Internal Medicine Service, Figueira da Foz Hospital, Figueira da Foz, Portugal.
authors.forename: Amélia
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Internal Medicine Service, Figueira da Foz Hospital, Figueira da Foz, Portugal.
authors.forename: Rosário
authors.initials: R
authors.lastname: Marinheiro
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal. Electronic address: rvitorino@ua.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Aveiro, Portugal; School of Health Sciences, University of Aveiro, Aveiro, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
mesh_terms: D015415:Biomarkers / Q000652:urine*; D048909:Diabetes Complications / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D003930:Diabetic Retinopathy / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D011507:Proteinuria; D040901:Proteomics; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D011506:Proteins